Tattoo removal using a liquid-gas mixture with plasma gas bubbles

ABSTRACT

Methods and systems are disclosed for removing a tattoo from a subject&#39;s skin by application of a cold plasma that is delivered via a liquid-gas mixture. The plasma can be delivered in the form of gas bubbles, in which at least a portion of gas is in the form of a plasma.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/938,694 filed on Jul. 24, 2020, the entire teachings of which areincorporated herein by reference.

FIELD

The present invention relates to methods and systems of skin treatmentand, in particular, tattoo removal, by applying a cold atmosphericplasma.

BACKGROUND

Permanent tattoos are created by piercing the skin with needles orsimilar instruments to mechanically deliver an ink, which includes smallparticles of pigments/dyes suspended in a carrier, into the dermal layerof the skin. The creation of a permanent tattoo requires theinsertion/implantation of pigments, dyes, and/or chromophores into thedermis which are not dissolvable and/or biodegradable. Followingmechanical insertion of the ink particles and during the healingprocess, the majority of the ink particles that remain in the dermis andthat have not otherwise been expelled from the skin or absorbed by thebody in the healing process, 70-80%, are engulfed by phagocytic skincells (such as fibroblasts and macrophages) or retained in theextracellular matrix of the dermis and the remaining ink particles arefound such that 10-15% of the ink particles lie flattened on collagenfibers and 5-10% of the ink particles lie attached on the serosal sideof capillaries.

Despite the wide acceptance and popularity of permanent tattoos, thereis a significant demand for the removal of tattoos. Removal of tattoos,however, represents a complex process that most typically involves theuse of lasers designed for aesthetic skin treatments and/or othermechanical removal techniques. The current state-of-the-art for tattooremoval is performed using a variety of lasers which induce degradationand absorption by the body of the inks to achieve tattoo removal. Thelaser conditions require matching the laser frequencies to the particlesaccording to their size, composition, color, and depth in the dermis.The laser is applied to the tattoo such that the pigments, dyes, and/orchromophores of the ink particles absorb the laser light and the laserpulses dissociate and degrade the pigments, dyes, and/or chromophorescomponents of the ink particles into small(er) fragments. The fragmentedink components may become small enough to be absorbed by the body andremoved from the dermis. Nonetheless, laser-based removal of tattoos hasseveral shortcomings. For example, lasers induce heating of the skin andcan cause burns as well as other undesirable tissue damage which cancause some scarring or color variations that are likely to remain afterhealing. Current laser-based procedures for tattoo removal may thereforebe somewhat ineffective at complete removal of tattoo inks, requiremultiple treatments at a high cost, cause pain, and can result inscarring, disfigurement, and depigmentation of the treated skin.

Therefore, it would be advantageous to provide a system and methods fortattoo removal using non-laser-based approaches. It would also beadvantageous to provide methods that enable removal/extraction of thedegraded ink components, such as dyes, pigments and other chromophores,from the body to reduce absorption by the body of potentiallyharmful/toxic chemicals.

It is therefore an object of the present teachings to provide a systemand method for removing a tattoo from a subject by degrading inkparticles trapped within the dermis.

It is an additional object of the present teachings to provide such asystem and method which allows for the extraction of the residue oftreated tattoo ink particles, which may have toxic properties, and ofother degradation components from the subject's skin tissues.

It is yet another object of the present teachings to provide methods forremoving tattoos which can be performed in one or more treatments andwhich are effectively less painful to the subject being treated thancurrent conventional methods of tattoo removal.

It is still a further object of the present teachings to provide methodsof tattoo removal which can address the limitations of currentstate-of-the-art removal methods (i.e., laser-based removal systems) toreduce issues with skin scarring, skin color bleaching, and residualtattoo shadowing remaining after removal treatment(s).

SUMMARY

Methods and systems are disclosed for removing a tattoo from a subject'sskin by application of a cold plasma that is delivered via a liquid-gasmixture. The plasma can be delivered in the form of gas bubbles, inwhich at least a portion of gas is in the form of a plasma.

In one aspect of the invention, methods of removing a tattoo from asubject's skin are disclosed comprising the steps of: (i) forming anactivated liquid-gas mixture comprising a liquid with plasma gasbubbles; (ii) delivering the activated liquid-gas mixture to a targettattoo region within a dermal region of the skin; whereby tattoo inkparticles can be dislodged by the application of said plasma to thetarget tattoo region.

The step of forming an activated liquid-gas mixture can further compriseactivating a liquid with entrained gas bubbles by applying a high energyelectric field to the liquid to induce plasma formation in the gasbubbles. Alternatively, the step of forming an activated liquid-gasmixture can further comprise applying a high energy electrical field toa gas to form a gas plasma and then mixing the gas plasma with a liquidto form the activated liquid gas mixture.

In certain embodiments, the plasma gas bubbles comprise a coldatmospheric plasma, wherein the plasma gas bubbles apply energy to thetarget tattoo region without raising the temperature of the targetregion more than 4 degrees C. The plasma gas bubbles can furthercomprise at least one gas selected from air, carbon oxide, oxygen,nitrogen, helium, argon. neon, xenon, and krypton. The liquid componentof the activated liquid-gas mixture can comprises at least one liquidselected from water, saline, and buffered aqueous solutions. In certainembodiments, the liquid-gas mixture can comprise water with dissolvedcarbon dioxide. The liquid component can also comprise one or moresurfactants, local anesthetics, anti-infective agents, antisepticagents, anti-inflammatory agents, or combinations thereof.

The activated liquid-gas mixture, sometimes referred to herein as fluidcold atmospheric plasma (F-CAP) can also be applied in conjunction witha gas-only cold atmospheric plasma (CAP). For example, the target tattooregion can be treated first by a CAP treatment, then by F-CAP, orvice-versa. Between CAP and F-CAP treatment, one or more additionalmobilization or extraction steps can be practiced. For further detailson CAP treatment, see commonly owned U.S. Pat. No. 10,716,611, hereinincorporated by reference in its entirety.

In addition to conveying the plasma gas bubbles to the target tattooregion of the dermis, the liquid component of the activated liquid-gasmixture can serve as a mobilization fluid such treatment oftattoo-containing cellular structures and mobilization of dislodgedtattoo ink particles occurs concurrently. Alternatively, the methods ofthe present invention can include the step of pretreating the targettattoo region by injecting the region with a separate mobilizationfluid. For example, injections of a fluid such distilled water or salinecan be delivered to the target tattoo region prior to plasma treatment.A series of blebs can be formed in the skin by such injections, whichcan assist in registration of the treatment apparatus and/or permitoutgassing of gas during or following treatment. The pretreatmentmobilization fluid that remains in the dermis can also facilitateextraction of dislodged or degraded ink particles following treatment.

The step of delivering the activated liquid-gas mixture to a targettattoo region can further comprise accessing the target tattoo regionvia at least one hollow needle inserted into the subject's skin. In someembodiments, multiple needles can be used to deliver the active liquidgas mixture. The liquid-gas mixture can be formed prior to plasmageneration, during plasma generation or following plasma generation. Forexample a concentric dual lumen tubular plasma generator can includeseparate passageways for the liquid (e.g., in an inner lumen) and thegas that will be ignited into a plasma (e.g., in an outer lumen). Theliquid and plasma can be mixed in the plasma generator, or at the entryinto a delivery needle or other treatment applicator or even in thedermis.

The method can further comprise applying suction to the target region,either via a separate device or via the treatment component. Forexample, dual lumen needles can again be employed with one lumenutilized to deliver the activated liquid-gas mixture and another lumenutilized to extract dislodged or degraded ink particles via suction.Extraction of the ink particles can be achieved via suction of amobilization fluid and/or suction of a natural bodily fluid containingthe particles from the target region.

The step of forming an active liquid-gas mixture can further compriseigniting a plasma in the gas component by a high strength electric fieldso that gas atoms are stripped of at least some of their orbitalelectrons. In certain embodiments, the plasma can be initiated byapplying an alternating electric field having at least one frequencyranging from about 1 kHz to 100 MHz. The plasma initiation step canfurther comprise delivering between about 0.1 and 10 microamperes, orbetween about 1 and 10 microamperes, of alternating current. The plasmainitiation step can also comprise applying a DC voltage between about 1and 10 kV, or between about 4 and 6 kV.

The method of the present invention can further comprise delivering aseparate mobilization fluid to the target region before, during or afterdelivering the activated liquid-gas mixture to a target tattoo region.This mobilization fluid comprises at least one of sterile water, asaline solution, or a buffered aqueous solution and optionally one ormore surfactants, local anesthetics, anti-infective agents, antisepticagents, anti-inflammatory agents, or combinations thereof.

In another aspect of the invention, A system for removing a tattoo froma subject's skin, the system comprising: (i) a gas source; (ii) a liquidsource; a plasma generator for generating an activated liquid-gasmixture comprising a liquid with plasma gas bubbles; and a conduit fordelivery of the activated liquid-gas mixture to target tattoo region.

The system can further comprise a mobilization fluid delivery componentfor delivering a liquid either from the liquid source or from analternative liquid source to the target tattoo region either before,during or after delivery of the activated liquid-gas mixture. In oneembodiment, the system can further comprise a syringe and needle todeliver of the mobilization fluid.

The system can also comprise an extraction component. In certainembodiments, the extraction component applies suction to the subject'stattooed dermis during or after the application of the activatedliquid-gas mixture with plasma gas bubbles.

The system can also include a treatment applicator configured to pierceskin and deliver the activated liquid-gas mixture to a tattoo region ina subject's dermis. For example, the treatment applicator can be ahollow needle with a tip, from which the activated liquid-gas mixture isapplied to the target tattoo region.

The hollow needle can be an single lumen needle or a multi-lumen, e.g.,a multiple sheathed, needle The treatment system can also include anarray of needles, each capable of delivering the activated liquid-gasmixture to the target tattoo region. The treatment applicator comprisesa removable, replaceable and/or disposable cartridge with one or moreneedles configured to penetrate the subject's tattooed skin.

In certain embodiments, the treatment applicator further comprises akinetic actuator that induces movement of the treatment applicatorduring treatment. For example, the kinetic actuator can cause an activetip of the applicator to penetrate and at least partially withdraw fromthe target region or to laterally vibrate within the target region,e.g., at a rate from about 0.01 Hz to 10 kHz, more preferably from about0.1 Hz to about 1 kHz, or at a rate of at least 10 times per minute.

The methods and systems of the invention apply energy in the form of acold plasma at a strength and duration to chemically degrade tattoo inkparticles. The applied energy can also rupture cell membranes of tattooink-bearing macrophages in the dermis and/or disrupt the extracellulardermal matrix to release tattoo ink particles entrapped within the cellsor extracellular matrix.

The plasma generator can be connected to a power supply, operating underthe control of a controller to deliver electrical energy capable ofigniting a plasma in at least some of the gas atoms or molecules. Theplasma can be formed by applying an alternating electric field having atleast one frequency ranging from about 1 kHz to 100 MHz. For example,the active electrode can deliver between about 0.1 and 10 microamperes,optionally between about 1 and 10 microamperes of alternating currentand/or a voltage between about 1 and 10 kV, optionally between about 4and 6 kV.

Alternatively or in addition, the power supply can supply electricalenergy to the plasma generator as a DC voltage. In certain embodiments,the power supply can deliver an pulsed DC current having a pulserepetition rate ranging from about 1 kHz to 100 MHz. For example, anactive electrode connected to the power supply can deliver DC pulses atbetween about 0.1 and 10 microamperes, optionally between about 0.1 and1 microamperes and/or at a voltage between about 1 and 10 kV, optionallybetween about 4 and 6 kV.

The plasma can be delivered without raising the temperature of thetarget region more than 4 degrees C.

The methods of the present invention preferably also includes the stepsof mobilizing and extracting dislodged or degraded ink particles. Forexample, the step of mobilizing ink particles can further comprisedelivering a mobilization fluid to the target region. The mobilizationfluid can include at least one of sterile water, a saline solution, or abuffered aqueous solution as well as one or more surfactants, localanesthetics, anti-infective agents, antiseptic agents, anti-inflammatoryagents, or combinations thereof. The extraction step can includeextracting ink particles via suction of a mobilization fluid or anatural bodily fluid containing the particles from the target region.

Systems according to the invention can further include an extractioncomponent and optionally a fluid delivery component. The system canfurther comprise a treatment applicator (e.g., a handpiece), which caninclude at least one fluid passageway for fluid delivery and/orextraction. The extraction component can apply suction to the subject'stattooed dermis during and/or subsequent to application of the plasmagas bubbles.

In some embodiments, the treatment applicator, the fluid deliverycomponent, the extraction component are integrated into a singletreatment component. The treatment component can be in the form of ahollow needle with a tip, from which the activated liquid-gas mixture isapplied to the target tattoo region. The hollow needle can be a multiplesheathed needle and, in certain embodiments, the treatment component cancomprises a cartridge unit with one or more needles which penetrate thesubject's tattooed skin. The cartridge unit can removable, replaceable,and/or disposable.

In some embodiments, cold plasma in the form of gas bubbles within aliquid delivery vehicle is applied via the treatment component to thetattooed dermis and surrounding tissue under the control of askilled/trained operator or technician and the treatment is applied witha high level of precision. In certain embodiments, all or a portion ofthe tattoo ink particles are dislodged or degraded, and extracted fromthe subject's tattooed dermis, to render the tattoo undetectable,invisible, and/or non-discernible to the naked eye.

Methods and systems using applied plasma to remove tattoos from asubject have been developed based on application of an alternatingcurrent (AC) or a pulsed direct current (DC) electric field to form agas plasma which can dislodge and degrade tattoo ink particles trappedwithin a subject's dermis to facilitate the removal of the mobilized inkparticles and/or degradation products thereof from the subject's dermisand surrounding tissues and render the tattoo invisible,non-discernible, and/or undetectable.

The plasma gas bubbles can be applied at a fluence and durationsufficient to chemically degrade tattoo ink particles, or at a fluenceand duration to sufficient disrupt the extracellular dermal matrix, orat a fluence and duration sufficient to rupture cell membranes of tattooink-bearing macrophages and release tattoo ink particles entrappedtherein.

Preferably, the plasma is applied without raising the temperature of thetarget region more than 4 degrees C. The plasma can also be applied inconjunction with electrical energy.

In certain embodiments, the method can further include the steps ofmobilizing and extracting dislodged or degraded ink particles. Forexample, degraded ink particles can be mobilized by delivering amobilization fluid to the target region. The mobilization fluid caninclude at least one of sterile water, a saline solution, or a bufferedaqueous solution, and optionally can further include one or moresurfactants, or one or more local anesthetics, anti-infective agents,antiseptic agents, anti-inflammatory agents, or combinations thereof.

The extraction step can include extracting degraded ink particles viasuction of a mobilization fluid or a natural bodily fluid containing theparticles from the target region. The method can also repeat themobilizing and extracting steps, or cycle the plasma application,mobilization and extraction steps. The treatment applicator and/ormobilization and extraction elements can also be in motion duringoperation, e.g., vibrating or oscillating in depth, to further augmenttheir function and/or expose a larger portion of the target region.

In certain embodiments, the system can also employ a plurality ofelectrodes disposed in an array with the electrodes separated from eachother by a distance sufficient to achieve a generally uniform electricfield over at least a portion of target region by overlapping fields. Insome embodiments, the electrode array can include multiple electrodesarranged in rows and/or columns, for example, at least 9 activeelectrodes, or optionally at least 16 electrodes, or optionally at least24 electrodes, arranged in a honeycomb pattern. The electrodes canaugment the application of F-CAP by providing additional energy to thetarget tattoo region.

The systems of the present invention can also include an extractioncomponent and optionally a fluid delivery component. When an extractioncomponent is utilized in the system, the extraction component canprovide suction or apply suction to the subject's tattooed dermis duringand/or subsequent to application of the F-CAP.

The plasma generator, the fluid delivery component, and the extractioncomponent can integrated into a treatment probe having at least onehollow needle with a tip, from which the plasma gas bubbles are appliedto the target tattoo region. At least one lumen within the probe canprovide mobilization fluid and/or suction to the target tattoo region.The hollow needle can further include a multiple sheathed needle, e.g.,with coaxial parallel lumens or concentric lumens to separate themobilization and extraction conduits.

The treatment component can take the form of a cartridge that can becoupled to a reusable hand piece. For example, the cartridge can includea plurality of needles which penetrate the subject's tattooed skin. Thecartridge unit can be removable, replaceable, and/or disposable.

Additionally, the system can further include a mechanical actuatoroscillator connected to the one or more active electrodes to permitmovement during operation, e.g., vibratory or oscillatory movement ofthe electrode during treatment.

In one preferred embodiment, F-CAP is applied to the subject's dermisvia one or more needles or probe-like structures that penetrate thesubject's tattooed skin. The plasma gas bubbles can be applied so thatthe energy interacts with constituents present within the dermis suchas, but not limited to, the tattoo ink particles themselves,macrophages, fibroblasts, cell membranes, collagen fibers, andcapillaries and other cellular and non-cellular constituents of thedermis which have trapped the tattoo ink particles in such a manner asto effectively disrupt the tissue components and dislodge the trappedtattoo ink particles. The plasma gas bubbles may also induce degradationof certain types of the ink particles, which are composed of organicand/or inorganic pigments, dyes, and/or chromophores and give color tothe ink particles. In preferred embodiments, the electrical energy bothdegrades and dislodges the trapped ink particles without causing anydamage or any significant amount of thermal or other type of irreparabledamage to the exposed dermis or other surrounding tissue.

In some embodiments, the cold plasma effectively dislodges and/ordegrades all or a portion of the tattoo ink particles during a single ormultiple tattoo removal treatment. Multiple treatments may be appliedwherein the number of treatments depends on factors such as the size andcomplexity of the tattoo and on the health of the individual and/orindividual's skin. As noted above F-CAP and CAP can be appliedsequentially together.

In some embodiments, the dislodged ink particles and degradationby-products thereof can be mobilized to remove them from the subject'sdermis and surrounding tissues prior to their recapture by the naturalprotection mechanisms of the skin, which can otherwise result in ashadowing effect or prior to their transport through the lymphaticchannels and deposition in lymph nodes.

In some embodiments, the mobilization step involves the delivery of apharmaceutically acceptable mobilization fluid which facilitates theremoval of the dislodged and degraded ink particles and by-productsthereof. The mobilization fluid delivered to the treated dermis isextracted in a subsequent extraction step such as by the application ofsuction. The extraction of the mobilization fluid containing thedislodged and degraded ink particles from the dermis and surroundingtissues removes the tattoo from the skin.

All or a portion of the dislodged and degraded tattoo ink particles andby-products thereof can be extracted from the subject's tattooed dermisduring an extraction step. By degrading, dislodging and removing thetattoo ink particles, the tattoo on skin treated according to the methoddescribed herein becomes undetectable, invisible, and/or non-discernibleto the naked eye. In certain other embodiments, the cold plasma candegrade all or a portion of the tattoo ink particles and the degradationby-products are converted into colorless components and the tattoobecomes undetectable, invisible, and/or non-discernible to the nakedeye. In such embodiments, treatment of the tattoo ink particles withapplied plasma gas bubbles may render the ink particles down to theircolorless atomic, molecular, and/or gaseous components, such as carbondioxide or water. In some embodiments, the colorless components may notneed to be removed or otherwise extracted from the skin if the tattoohas otherwise been rendered undetectable, invisible, and/ornon-discernible to the naked eye. In other embodiments, the dislodgedand degraded ink particles and degradation by-products thereof which arerendered into colorless components may be absorbed by natural processesfrom the interstitial fluid of the dermis or elsewhere in the body.

The extraction of the degraded and dislodged ink particles andby-products thereof from the subject's skin is advantageous as the inkparticles, components and degradation by-products thereof may have toxicproperties which can potentially have harmful effects if absorbed by thesubject's body.

In another embodiment, a system for removal of tattoos using appliedelectrical energy is formed of (1) an F-CAP generation component; (2) anoptional auxiliary fluid delivery component; and (3) a fluid extractioncomponent. The F-CAP component is coupled and connected to a treatmentcomponent for delivery of the electrical energy to the tattooed dermisof a subject. The fluid delivery component of the system deliversmobilization fluid to the treatment component which in turn is used todeliver the fluid to the tattooed dermis and surrounding tissue. Themobilization fluid is formed of a pharmaceutically acceptableformulation and facilitates the removal of dislodged and degraded tattooink particles and degradation by-products thereof and tissue degradationby-products formed or created during or after exposure to the electricalenergy.

The fluid extraction component of the system can be coupled andconnected to the treatment component to provide suction for extractionof the mobilization fluid and/or removal/extraction of dislodged anddegraded tattoo ink particles which may be present in the natural fluidspresent in the dermis or surrounding tissue directly.

In some embodiments of the system, the F-CAP component, an optionalkinetic applicator, fluid delivery component, and a fluid extractioncomponent may be incorporated into a combined free-standing treatmentinstrument or system. In some embodiments. the fluid delivery and/orextraction components can be excluded from the combined treatmentinstrument.

These and other features of the applicant's teachings are set forthherein.

BRIEF DESCRIPTION OF THE DRAWINGS

The skilled person in the art will understand that the drawings,described below, are for illustration purposes only. The drawings arenot intended to limit the scope of the applicant's teachings in any way.

FIG. 1 is a schematic illustration of tattoo removal by cold plasmausing a liquid with entrained gas according to the invention.

FIGS. 1A-1D shows a non-limiting example of one method for tattooremoval according to invention. FIG. 1A show a tattoo in which inkparticles are entrapped within dermal tissue structures. FIG. 1B thesteps of dislodgement of intra-cellularly trapped tattoo ink particleswith a cold atmospheric plasma, mobilization of the dislodged anddegraded ink particles, and extraction of the ink particles for removalof a tattoo from a subject's dermis and surrounding tissue.

FIG. 2 is a schematic illustration of a tattoo removal system capable ofapplying an activated liquid-gas mixture to a target tattoo region.

FIG. 3 shows another non-limiting example of a tattoo removal systemcapable of applying an activated liquid-gas mixture to a target tattooregion.

FIG. 3A is a schematic illustration of a kinetic applicator for use withsystems according to the invention.

FIG. 4 shows a non-limiting example of a treatment component in the formof a pen or wand which includes a treatment end which contains one ormore needle or probe-like structures as part of a disposable cartridge.

FIGS. 4A and 4B show front (4A) and side (4B) views of a multi-sheathedneedle or probe-like structure formed of three concentricnested/embedded needle or probe-like structures forming inner, middle,and outer rings. The outer portion of the needle or probe-like structureincludes optional openings.

FIGS. 5A and 5B show front (5A) and side (5B) views of a multi-sheathedneedle or probe-like structure formed of two concentric nested/embeddedneedle or probe-like structures forming inner and outer rings. The outerportion of the needle or probe-like structure includes optionalopenings.

FIGS. 6A and 6B show front (6A) and side (6B) views of a single-sheathedneedle. The outer portion of the needle or probe-like structure includesoptional openings.

FIGS. 7A-7C illustrate the used of an array of electrodes that can beused in conjunction with F-CAP treatment. The electrodes can beseparated from each other to achieve a generally uniform electric fieldstrength over at least a portion of a target region by overlappingfields. FIG. 7A illustrates a two electrode array and the respectiveelectric fields when electrical energy is applied to the individualelectrodes. FIG. 7B is a graph of electrical field intensity versusdistance from each electrode and further illustrating (by a dotted line)to increased field uniformity due to the overlapping fields. FIG. 7Cillustrates a multi-electrode array with electrodes in a “honeycomb”arrangement to further enhance field uniformity.

FIG. 8 shows another non-limiting example of a tattoo removal systemcapable of applying an activated liquid-gas mixture to a target tattooregion.

FIG. 9 shows yet another non-limiting example of a tattoo removal systemcapable of applying an activated liquid-gas mixture to a target tattooregion.

It should be understood that a number of modifications can be made tothe system and/or components shown in the Figures. For the purposes ofclarity. not every component is labeled in every illustration of thesystem and/or components as shown in the figures. nor is every componentof each embodiment shown where illustration is not required to allow oneof ordinary skill to understand the system and/or components.

DETAILED DESCRIPTION

Various terms relating to aspects of the present disclosure are usedthroughout the specification and claims. Such terms are to be giventheir ordinary meanings in the art, unless otherwise indicated. In orderfor the present disclosure to be more readily understood, certain termsare first defined below. Additional definitions for the following termsand other terms are set forth throughout the specification.

As used herein, the terms “about” and “approximately” are used asequivalents. Any numerals used in this application with or withoutabout/approximately are meant to cover any normal fluctuationsappreciated by one of ordinary skill in the relevant art. In certainembodiments, the term “approximately” or “about” refers to a range ofvalues that fall within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%,12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less in eitherdirection (greater than or less than) of the stated reference valueunless otherwise stated or otherwise evident from the context (exceptwhere such number would exceed 100% of a possible value).

As used herein, unless otherwise clear from context, the term “a” may beunderstood to mean “at least one.” As used in this application, the term“or” may be understood to mean “and/or.” In this application, the terms“comprising” and “including” may be understood to encompass itemizedcomponents or steps whether presented by themselves or together with oneor more additional components or steps.

As used herein, the term “bubble” is used to describe the gas componentof the activated liquid-gas mixture. The bubbles can be visible or sosmall as to be invisible, e.g., dissolved gas molecules. The bubbles cantake to form of a foam or be part of turbulent liquid-gas flow. However,within the bubbles at least a portion of the gas molecules have beenexcited to a “plasma” state in which individual atoms or molecules havebeen stripped of at least some of their orbital electrons.

“Connected,” and “coupled,” as used herein, refers to directly coupling(i.e., connecting) one element (i.e., output) of a system or componentto another element (i.e. input) by any suitable means available, suchas, for example, through tubing. Optionally, other intervening elementsmay also be present.

“Color,” as used herein, is broadly defined as a detectable propertydetermined by a substance's electromagnetic absorption and/or emissionin the visible spectrum.

“Colorless,” as used herein, refers to when essentially no color can bedetected apart from the normal coloration of the surroundings (such asskin or other tissue) by the naked eye under normal lighting conditions,for example, diffuse sunlight or standard artificial lighting.

“Dielectric barrier” discharge as used herein refers to an electricaldischarge between electrodes separated by a dielectric material. Forexample, one or both electrodes can be coated with a dielectricmaterial.

“Dislodged,” as used herein, refers to the release of tattoo inkparticles from local skin cells and tissue structures such as cells,membranes, and/or tissues, typically found in the dermis. As usedherein, “Dislodge,” “Dislodged,” “Dislodgement,” or other variationsalso encompass degradation of tattoo ink particles.

“Degrade,” “Degraded,” “Dislodgement,” and the like as used herein,refers to the dislodgement of tattoo particles by the breakdown of theorganic and/or inorganic components of tattoo ink particles due tointeraction with the applied cold plasma energy via processes thatinclude, but are not limited to, oxidation, reduction, fragmentation,electron decomposition, ion decomposition, or other degradationpathways. Degradation generally refers to a breakdown of a coloredorganic pigment, dye, or chromophore and/or to the breakdown of theparticle size of colored inorganic ink particles which causes them tobecome colorless. Degradation can come about through the disruption ofcrystals or amorphic masses of elements such carbon, or by the breakingof chemical bonds in organic or inorganic compounds.

“Pigment, dye, or chromophore,” as used herein, are terms that refer toorganic and/or inorganic substance(s) which are colored and impart colorto a tattoo ink. The color may result from substances which containheavy metals such as mercury (red), lead (yellow, green, white), cadmium(red, orange, yellow), Chromium (green), cobalt (blue), aluminum (green,violet), titanium (white), copper (blue, green), iron (brown, red,black), barium (white), substances which contain metal oxides such asferrocyanide and ferricyanide (yellow, red, green, blue), substancessuch as organic chemicals/compounds such as azo-containing chemicals(orange, brown, yellow, green, violet), naptha-derived chemicals (red),substances such as carbon (i.e., soot or ash) for black ink, and othercolor compounds which may contain antimony, arsenic, beryllium, calcium,lithium, selenium and sulfur. The pigments, dyes, or chromophores of atattoo ink are typically dispersed or suspended in a carrier mediumwhich together are delivered to the dermis. The most typical carrierconstituents are ethyl alcohol and water, but may be denatured alcohols,methanol, rubbing alcohol, propylene glycol, and/or glycerin.

“Plasma,” as used herein connotes a state of matter in which one or moreatoms or molecules have been subjected to sufficient energy to strip atleast some of their orbital electrons. The transition from gas to plasmais also referred to as ionization.

“Invisible,” as used herein, refers to the state of tattoo inks thatshow essentially no color which can be detected (such as in a tissue)apart from the normal coloration of the surroundings (such as skin orother tissue) by the naked eye under normal lighting conditions, forexample, diffuse sunlight or standard artificial lighting.

“Non-discernible and undetectable,” are used interchangeably and referto a substance (i.e., tattoo ink) rendered invisible to the naked eyeunder normal lighting conditions, and also invisible to the naked eye,or a device, under any other lighting conditions.

“Removal” of a tattoo as used herein refers to any reduction of thevisible appearance of a tattoo. Removal can mean rendering a tattoonon-discernible and undetectable or simply rendering a tattoo lessnoticeable in its appearance.

“Substantially” refers to a qualitative condition of exhibiting total ornear-total extent or degree of a characteristic or property of interest.One of ordinary skill in the art will understand that electricalproperties rarely, if ever, go to completion and/or proceed tocompleteness or achieve or avoid an absolute result. Substantially istherefore used herein to capture a potential lack of completenessinherent therein. Values may differ in a range of values within 25%,20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%,5%, 4%, 3%, 2%, 1%, or less in either direction (greater than or lessthan). For example, values may differ by 5%.

“Tattoo,” as used herein, refers to a portion of skin, typically thedermis, which has tattoo ink particles embedded or trapped within.

“Uniform” refers to a qualitative condition of exhibiting similarity ina characteristic or property of interest. “Uniform” is therefore usedherein to capture a degree of substantial similarity. Values may differin a range of values within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%,12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less in eitherdirection (greater than or less than). For example, values may differ by5%.

The methods for tattoo removal described herein are based on applicationof a DC pulsed or high frequency AC at a sufficient strength andduration to form plasma gas bubbles capable of dislodging or degradingtattoo ink particles trapped within a subject's dermis and extraction ofthe mobilized particles and/or degradation products from the subject'sdermis. The method includes the steps of: (i) dislodging and/ordegrading tattoo ink particles by applying electrical energy to asubject's tattooed dermis; (ii) mobilizing the dislodged and/or degradedink particles and by-products thereof; and (iii) extracting thedislodged and/or degraded ink particles and by-products thereof from thesubject's dermis to render the tattoo undetectable, invisible, and/ornon-discernible.

FIG. 1 illustrates a process according to the invention in which aneedle 20 is used to pierce the epidermis 11 and deliver plasma gasbubbles 32 to a target tattoo region with the dermis 12. In this region,tattoo ink particles 14 are present (typically entrapped in cellularstructures 16). The needle delivers an activated liquid-gas mixture tothe target region such that plasma gas bubbles can act upon the cellularstructures that are holding the ink particles and dislodge and/ordegrade them.

As further illustrated in FIGS. 1A-1D, the activated liquid gas mixtureis delivered to the tattooed dermis 12 of a subject and inducesdislodgement of ink particles 14 trapped by the cells, membranes, and/orother tissue structures 16 of the dermis 12 which are holding the inkparticles 14 in place. The plasma (e.g., plasma gas bubbles can bedelivered by any suitable means known. In preferred embodiments theplasma 10 is delivered to the dermis 12 via one or more needle orprobe-like structures 20 that can penetrate the subject's tattooed skin.Those skilled in the art will be able to determine the penetration depthof the one of more needle or probe-like structures to deliver the plasmato the tattooed dermis.

It is believed that the plasma gas bubbles delivered to a subject'stattooed dermis interact with constituents present within the dermissuch as, but not limited to, macrophages, fibroblasts, other cells,collagen fibers, and capillaries which have trapped the tattoo inkparticle, in a sufficient amount to effectively disrupt the local dermalskin cells and tissue structures holding the particles and dislodge thetrapped tattoo ink particles from the dermis and surrounding tissues.The plasma also may induce degradation of the ink particles, which arecomposed of organic and/or inorganic pigments, dyes, and/or chromophoresand give color to the ink particles. Such degradation can result fromthe interaction of the plasma with the organic and/or inorganiccomponents of the ink particles to degrade them via such processes asoxidation, reduction, fragmentation, electron decomposition, iondecomposition, or other degradation pathways.

In preferred embodiments, the plasma both dislodges the trapped inkparticles without causing a significant amount of thermal or other typeof irreparable damage to the subject's dermis or surrounding tissue.

In some embodiments of the method, the exposure time of the dermis tothe plasma gas bubbles needed to dislodge and degrade the tattoo inkparticles can be as short as one microsecond, but is more preferably alonger period of time, in the range from about one microsecond up toabout one hour. In some embodiments, the plasma effectively degrades anddislodges the ink particles at the point of exposure within a period oftime of 60 minutes or less, more preferably 10 minutes or less. Incertain embodiments, the plasma may effectively dislodge and degrade allor a portion of the tattoo ink particles within a single tattoo removaltreatment. In other embodiments, multiple treatments using plasmaaccording to the methods described may be applied. The number oftreatments depends on factors such as the area/size and complexity ofthe tattoo (for example, multi-colored and/or multi-layered tattoo andthe age and settling of tattoo inks into lower portion of dermis overtime) and on the health of the individual and/or individual's skin. Insome non-limiting embodiments, tattooed skin having an area of up to 5square inches may be treated in as little as one treatment. For tattooshaving a larger surface area/size and/or complexity, repeated treatmentsmay be applied with an intervening period time passing betweentreatments, such as up to one week, up to two weeks, up to three weeks,up to one month, up to two months, or up to three months; longer periodsof time may pass between treatments as needed. In preferred embodimentsof the method, the temperature of the dermis or other surroundingtissues is not increased by exposure to the plasma.

In certain other embodiments, the temperature of the dermis or othersurrounding tissues when exposed to a treatment is not increased at allor significantly, only increasing by about 1° to about 5° C. abovenormal body temperature. which is below the temperatures needed toinduce any significant amount of thermal damage or pain. The applicationof plasma to the dermis for tattoo removal is not expected to produceblanching and/or bleaching of the subject's natural skin color orpigmentation.

Referring again to FIG. 1 and FIGS. 1A-1D, the dislodged ink particles14, and/or degradation by-products thereof, are mobilized in amobilization step to remove them from the subject's dermis andsurrounding tissues 12 prior to their recapture by the naturalprotection mechanisms of the skin, which can result in a re-tattooingeffect. In some embodiments, the mobilization step involves the deliveryof a pharmaceutically acceptable mobilization fluid 24, preferablythrough the same one or more needle or probe-like structures used todeliver the plasma 22. The mobilization fluid 24 facilitates the removalof the dislodged and degraded ink particles 14 and by-products thereoffrom the dermis 12. The mobilization fluid delivered to the plasmatreated dermis is extracted in a subsequent extraction step which can beaccomplished by any suitable means, such as by the application ofsuction. Suction, as used herein, refers to at least a partial vacuumcreated at the ends of the one or more needle or probe-like structuresdescribed above, such that the mobilization fluid containing thedislodged and degraded ink particles 26 is drawn away and extracted fromthe dermis and surrounding tissues. In some embodiments, suction isapplied as a continuous suction or, alternatively, suction can beapplied as a non-continuous pulsing suction. In some embodiments, nomobilization fluid is administered during or after the treatment and thedislodged ink particles and degradation by-products thereof are removedby extraction (i.e., suction) of natural bodily fluid(s) containing theparticles and by-products from the dermis and/or surrounding tissueduring the extraction step.

In preferred embodiments, all or a portion of the dislodged and/ordegraded tattoo ink particles are extracted from a tattoo during theextraction step. By removing dislodged and degraded tattoo inkparticles, the tattoo on skin treated according to the method describedbecomes undetectable, invisible, and/or non-discernible. By definition,an effective amount of plasma is applied to cause the colors in theoriginal tattoo in the treated area to become undetectable, invisibleand/or non-discernible. In some embodiments, treatment of the tattoo inkparticles with plasma may render the ink particles down to theircolorless atomic, molecular, and/or gaseous components, such as carbondioxide or water, and the colorless components may not require removalor extraction from the skin if the tattoo has otherwise been renderedundetectable, invisible, and/or non-discernible to the naked eye. Insuch embodiments, the portion of dislodged and degraded ink particlesand degradation by-products thereof which are rendered into colorlesscomponents and which remain in the dermis may be absorbed through theinterstitial fluid of the body. In such embodiments the method involvesdislodging and degrading tattoo ink particles by applying plasma to asubject's tattooed dermis; wherein the energy is applied in an effectiveamount to a subject's dermis to render the tattoo undetectable,invisible, and/or non-discernible.

The application of the steps of mobilizing the dislodged and/or degradedink particles and by-products thereof and extracting the dislodgedand/or degraded ink particles and by-products thereof from the subject'sdermis as described above are optional and determined at the discretionof the skilled technician or operator applying the tattoo removal methodto the subject's tattooed skin. Depending on the extent to which thetattoo has been rendered undetectable, invisible, and/or non-discernibleby plasma treatment alone the operator/technician may apply steps (ii)and (iii) as shown in FIG. 1 in order to further render the tattooundetectable, invisible, and/or non-discernible.

In some embodiments, the extraction of the degraded and/or dislodged inkparticles and by-products thereof from the subject's skin is highlydesirable as these may have toxic properties. In contrast to laser-basedtattoo removal techniques wherein inks and degradation by-productsthereof may remain in situ and/or become absorbed by the subject's body,the methods described herein can result in extraction of these foreigninks and components in order to prevent their absorption by the subjectand any potentially harmful effects on health.

In some embodiments of the method the steps of dislodgement,mobilization, and extraction, as shown in FIG. 1 , are performed insequence as shown, for example, (i)→(ii)→(iii). In embodiments whereinthe steps are applied sequentially, the steps are performed so as toprovide at least one complete cycle which includes the dislodgement,mobilization, and extraction steps (i), (ii), and (iii). The completecycle may be repeated any number of times as necessary to effectivelyremove the tattoo by dislodging and degrading tattoo ink particles fromthe subject's dermis and tissue. The preferred number of cycles whichmay be applied are typically in the range of one to 100 cycles, or more.

In certain other embodiments, all of the steps are applied concurrently.In a non-limiting example, the dislodgement (application of plasma totattooed dermis), mobilization, which may include the introduction of amobilization fluid to the dermis, and the extraction step, whichinvolves removal of the mobilization fluid containing the dislodged anddegraded ink particles and degradation by-products thereof, or in someinstances where no mobilization fluid is used, removes the dislodged anddegraded ink particles and degradation by-products thereof directly.

In some other embodiments, the steps of dislodgement and mobilizationoccur concurrently and are followed by the extraction step and form acycle which is performed at least one or more times, as necessary toremove the tattoo ink from the subject's dermis and rendering the tattooundetectable, invisible, and/or non-discernible.

In certain embodiments, the method described above can further include apretreatment of the surface of the tattooed skin with a mobilizationfluid, e.g., water saline or the like. In certain embodiments, anantibiotic solution can be pre-applied in order to prevent theintroduction of infectious organisms present on the surface to the skininto the dermis during treatment. In other embodiments, the pretreatmentmay also include application of topical anesthetics to the surface ofthe skin in order to prevent or alleviate any potential discomfortduring the treatment.

In some embodiments, electrical energy can be applied in conjunctionwith “cold plasma” that, as used herein refers to a non-thermal oratmospheric plasma, generated by subjecting a gas(es) to a strongelectrical field with a rapidly changing polarity to create a plasmawhich may contain electrons, highly energetic positively or negativelycharged ions, and chemically active species such as ozone, hydroxylradicals, nitrous oxides and other excited atoms or molecules. Inparticular, cold or non-thermal plasmas are created at or near standardatmospheric pressure and have temperatures which are close to or nearroom temperature which are non-damaging when applied to tissue.Contacting tissue with a cold plasma does not increase the tissuetemperature at all or significantly, typically only by a few degrees orless.

Methods for generating cold plasma as described herein arewell-understood by those skilled in the art. Exemplary methods toproduce atmospheric cold plasmas include, but are not limited to, arcdischarge, corona discharge. dielectric barrier discharge (DBD).capacitive discharge. and piezoelectric direct discharge. Typically,such plasmas are generated from a gas or a mixture of gases whichinclude, but are not limited to, air. oxygen, nitrogen, helium, argon.neon, xenon, and krypton. In certain embodiments. the cold plasma isgenerated from a mixture of argon and oxygen or a mixture of helium andoxygen. Conditions such as the power, flow rate of gas(es), and theratio of gases in mixtures used to generate a cold plasma can beoptimized as needed to achieve the desired properties of the coldplasma, such as to ensure it is at or near room temperature.

In certain embodiments the power used to generate the plasma is in therange of about 80 W to about 150 W. In some preferred embodiments, thegas flow rates are in the range of about 0.00001 to about 15 L min⁻¹.The relative percentages of the one or more gases present in the mixturecan be any suitable relative percentage necessary to achieve a coldplasma. In preferred embodiments, wherein the plasma generating mixtureof gases is composed of oxygen mixed with argon or helium, thepercentage of oxygen in the mixture is preferably in the range of about0.1% to about 5%.

The cold plasma stream generated according to the methods describedherein may be delivered and output into the dermis via one or moreneedle or probe-like structures as a continuous cold plasma jet streamor can be delivered as a discontinuous pulsed cold plasma jet stream. Itshould be apparent that the details described herein are non-limitingand that other suitable conditions and parameters can be selected andutilized in order to generate and deliver the cold plasma to the dermis.

In certain embodiments, non-limiting examples of the mobilization fluidinclude sterile water, saline solution, or buffered aqueous solutions.One skilled in the art can readily determine a suitable saline andbuffer content and pH for a mobilization fluid/solution to beadministered to the dermis of a subject. Representative examples includephosphate buffered saline (“PBS”), Ringer's solution, and sterilephysiological saline (0.15 M NaCl).

In certain embodiments, the mobilization fluid can further includesurfactants which improve the mobility and removal efficiency of thedegraded ink particles and/or degradation by-products thereof. Preferredsurfactants include those approved by the U.S. Food and DrugAdministration (“FDA”) as GRAS (“generally regarded as safe”) excipientsfor injection. In certain other embodiments, the mobilization fluid canalso include suitable local anesthetics, anti-infective agents,antiseptic agents, anti-inflammatory agents, and combinations thereof.

Surfactants which can be included in the mobilization fluid may beanionic, cationic, amphoteric, and non-ionic surfactants which arepharmaceutically acceptable for use in a human subject. Anionicsurfactants include di-(2 ethylhexyl)sodium sulfosuccinate; non-ionicsurfactants include the fatty acids such as butyric acid, valeric acid,caproic acid, enanthic acid, caprylic acid, pelargonic acid, caprylicacid, undecylic acid, lauric acid. tridecylic acid, myristic acid,pentadecylic acid, palmitic acid, heptadecylic acid, stearic acid,nonadecanoic acid, arachic acid, isocrotonic acid, undecylenic acid,oleic acid, elaidic acid, sorbic acid, linoleic acid, linolenic acid,arachidonic acid and esters thereof; surfactants in the amphoteric groupinclude substances classified as simple, conjugated and derived proteinssuch as the albumins, gelatins, and glycoproteins, and substancescontained within the phospholipid classification. Amine salts andquaternary ammonium salts within the cationic group also comprise usefulsurfactants. Synthetic polymers may also be used as surfactants andinclude compositions such as polyethylene glycol and polypropyleneglycol. Hydrophobic surfactants can be used to improve the removal ofhydrophobic ink particles and degradation by-products thereof.Hydrophilic surfactants can be used to improve the removal ofhydrophilic ink particles and components and degradation by-productsthereof. Amphiphilic surfactants can be used to improve the removal ofamphiphilic ink particles and components and degradation by-productsthereof.

In some embodiments, anesthetic agents can be included in themobilization fluid such as local anesthetics, such as but not limitedto, caine anesthetics such as bupivacaine, ropivacaine, dibucaine,procaine, chloroprocaine, prilocaine, mepivacaine, etidocaine,tetracaine, lidocaine, and xylocaine, and mixtures thereof which can beused alone or in combination with other analgesics.

In some embodiments, antiseptic agents can be included in themobilization fluid. Exemplary antiseptic agents can be composed of anyanti-infective compound that prevents the growth of and/or killsinfectious organisms. Antiseptic agents are preferably non-irritatingand hypoallergenic, such that they do not cause any adverse reactions tothe dermis and surrounding tissue of the subject.

“Anti-infective agent,” as used herein, refers to common antibacterial,antifungal, and antiviral agents which can be include a chemicalsubstance or group of chemical substances that inhibit the growth of, ordestroy microorganisms, fungi, and viruses and are used chiefly in thetreatment of infectious diseases. In some preferred embodiments,antibiotics can be included in the mobilization fluid. These may help toprevent infection in the dermis and surrounding tissues of the site oftattoo removal. Exemplary antibiotics include, but are not limited to,chloramphenicol, chlortetracycline, clindamycin, erythromycin,gramicidin, gentamicin, metronidazole, mupiroicin, neomycin, polymyxinB, bacitracin, doxycycline, ampicillin, penicillin, silver sulfadiazine,tetracycline, erythromycin, or combinations thereof.

In some embodiments, anti-inflammatory agents can be included in themobilization fluid. Anti-inflammatory agents can provide beneficialeffects during tissue healing and repair. Anti-inflammatory agents caninclude, but are not limited to, steroidal anti-inflammatory agents suchas dexamethasone, budesonide, beclomethasone, and hydrocortisone andnon-steroidal Anti-Inflammatory Agents (NSAIDS). NSAIDS typicallyinhibit the body's ability to synthesize prostaglandins. Prostaglandinsare a family of hormone-like chemicals, some of which are made inresponse to cell injury. Specific NSAIDS approved for administration tohumans include naproxen sodium, diclofenac, sulindac, oxaprozin,diflunisal, aspirin, piroxicam, indomethacin, etodolac, ibuprofen,fenoprofen, ketoprofen, mefenamic acid, nabumetone, tolmetin sodium, andketorolac tromethamine. Anti-Inflammatory agents are a well-known classof pharmaceutical agents which reduce inflammation by acting on bodymechanisms (Stedman's Medical Dictionary 26 ed., Williams and Wilkins,(1995); Physicians' Desk Reference 51 ed., Medical Economics, (1997)).

In some embodiments, the mobilization fluid may further containadditional agents, such as preservatives, viscosity adjusting additives,and other potentially beneficial materials, such hydrogen peroxide orhemoglobin derived oxygen carriers. Any volume of the formulatedmobilization fluid may delivered as needed to the treated dermis inorder to effectively facilitate removal of the dislodged and degradedink particles and by-products thereof during the extraction step. Inpreferred embodiments the total volume of mobilization fluid used toremove dislodged and degraded ink particles and degradation by-productsthereof is less than about 10 mL, more preferably less that about 5 mL,even more preferably less than about 2 mL, and most preferably less thanabout 1 mL.

Plasma Generating Component

In one non-limiting embodiment as shown in FIG. 2 . a system 50 is shownincluding liquid source 52, a gas source 54 and a mixer 56. The systemcan optionally include a pump 58 and/or a temperature regulator 60. Thesystem can be operated under the control of a controller 62. The systemcan operation. in one example, to deliver a liquid-gas mixture to afirst end of plasma generator including a tubular element 51. Togenerate a plasma within the gas component. a power source 64 (alsounder control of the controller 62) delivered a DC and/or AC current toone or more electrodes 65. In certain embodiments. the electrode can bea dielectric barrier discharge electrode. In other embodiments. thedischarge can be induced by a piezoelectric transducer.

The system can further include an optional vacuum source 68 to extractdislodged and/or degraded tattoo ink particles. (The vacuum or suctionsource can also be a stand alone instrument in some embodiments of thesystem).

The system can further include an alternative liquid supply 66. Thisalternative liquid supply can provide an additional source ofmobilization fluid that can be provided to the target tattoo regionbefore, during or after plasma treatment. In another embodiment, plasmagenerator can act first on gas from gas source 54 to generate a gasplasma which is then mixed with a liquid component at or near the exitend of the plasma generator to create the activated liquid-gas mixture.

The activated liquid-gas mixture can then be delivered to treatment head20, e.g., one or more hollow needles configured to penetrate theepidermis 11 and deliver the plasma to the dermis where it can act upontattoo ink particles 14 and/or cellular structures 16 m in which the inkparticles are embedded, encased or otherwise bound.

In the present invention, cold plasma is generated in mixture of atleast one liquid and at least one gaseous substance. The cold plasma canbe formed by corona discharge or dielectric barrier discharge.

An apparatus for generating cold plasma via excited gas bubbles cancomprise a plasma discharge unit with a first end and a second end. Asource of liquid and a source of gas can be fed into a mixing unitarranged upstream of the first end of the plasma discharge unit todeliver the liquid with entrained gas to the discharge unit. The secondend of the discharge unit can be coupled to a hollow needle or array ofneedles to deliver the liquid with cold plasma gas bubbles to a targetsite. In certain embodiments, the plasma discharge unit is tubular. Thedischarge unit and the needle or needle array can be integrally formedtogether.

In the exemplary embodiment of FIG. 2 , one or more electrodes arecoupled to an outer wall of a discharge unit for generating a highenergy alternating electric field within the discharge unit. Thecontroller 52 is connected at least to the mixing unit 56 and theelectrodes 65. The controller 52 can determine the proportions of the atleast one gaseous substance and of the at least one liquid substance orof the various liquid substances in the mixing unit, so that a desiredmixture enters the plasma discharge unit. The controller can also adjustthe voltage applied to the electrodes. From the mixing unit, the mixtureof at least one gaseous substance and at least one liquid substance canbe pumped into the discharge unit at the first end. The transfer intothe tubular discharge unit by means of the pump can also be controlledby the controller.

The applied alternating electric field is preferably strong enough thata cold gas discharge can be ignited inside the gas bubbles in the liquidin the plasma discharge unit. The intensity of the interaction can becontrolled by the amplitude and frequency of the applied alternatingelectric field, the mixing ratio and the total surface area of theinterfaces between the gaseous and liquid phases. Many liquids have adielectric constant significantly greater than 2. Typical gases have adielectric constant of nearly 1. Water, for example, has a dielectricconstant of 80. This difference in dielectric constant between a gaseoussubstance and a liquid substance can cause a sharp drop in the appliedelectrical potential in the gas bubble. As a result, the electric fieldstrength in the gas bubbles is particularly high.

In certain embodiments, the mechanism for generating the alternatingelectric field within the tubular discharge unit can be a piezoelectrictransducer or transformer. In other embodiments the mechanism can be adielectric barrier electrode. In either embodiment, at least oneelectrode is coupled to the plasma discharge unit. The electrode can beconnected to a voltage source and the voltage applied is controlled bythe controller 52. An electric field can be formed within the dischargeunit by the at least one electrode 65.

The electric field can extend beyond the second end of the tubulardischarge unit. This allows the discharge area to extend beyond thesecond end of the discharge unit or beyond a needle or other treatmentapplicator 20 provided at the second end of the discharge unit.

The treatment applicator can be configured in such a way that a spray atthe second end of the tubular discharge unit, or at the end of a needleor nozzle, is dispersed or atomized by electrostatic charging. Incertain embodiments, the spray is delivered to a tattooed region of thedermis.

The mixing unit may be connected to at least one source or reservoir forthe at least one gaseous substance and to at least one source orreservoir for the at least one liquid substance. A plural reservoirs forthe liquid and/or gaseous substance can be connected to the mixing unit.

A temperature control device (a heater or cooling unit) 60 can also beto the tubular discharge unit by means of which the active species inthe tubular discharge unit can be heated and/or cooled. With thetemperature control device 60, the temperature of the mixture of the atleast one gaseous substance and the at least one liquid substance in thetubular discharge unit can thus be brought to a predetermined value. Intattoo removal applications, the discharge can be controlled such thatthe plasma is maintained at or near room temperature (e.g., a coldplasma). The discharge unit can be fluidly connected to a target tattooregion via the second end directly or via a delivery device, such as oneor more hollow needles, a nozzle or a cannula.

The inventive method for degrading tattoo ink particles can becharacterised in that at least one gaseous substance is mixed with atleast one liquid substance in a mixing unit. The mixture passes from themixing unit into a first end of a plasma discharge unit. The mixture canbe pumped from the mixing unit into the first end of the discharge unit.In the discharge unit, bubbles of the gaseous substance are exposed toan intense electric field. In certain embodiments, a controllergenerates an alternating electric field which is applied to the mixtureof the at least one gaseous substance and of the at least one liquidsubstance. The gas discharge is ignited in the bubbles formed by thegaseous substance. The mixing ratio of the at least one gaseoussubstance and the at least one liquid substance can be adjusted or setby the controller. The controller 52 can also set the applied strengthof the alternating electric field. The mixing ratio and the totalsurface area of the interfaces between the gaseous and liquid phases canbe adjusted by means of the intensity of the interaction, the amplitudeand the frequency of the applied alternating electric field. The activespecies generated by the alternating electric field are fed to a targettattoo region via a second end of the discharge unit.

The intensity of electric field generated within the plasma dischargeunit can be controlled by adjusting a DC voltage source. The gaseousand/or liquid substance can be forced through the needle or needle arrayin such a way that a stream or dispersed spray is delivered to a targetdermal region where tattoo ink particles are located. The flow of liquidwith entrained plasma gas bubbles from the needles or tubular dischargeunit can be continuous or discontinuous.

The inventive methods can be employed to stimulate the skin and/orsubcutaneous areas with an alternating electric field and the coldplasma. It is also possible to flush a subcutaneous cavity with anactivated liquid or mixture of different liquids (liquid substances) oran activated gas mixture or a mixture of at least one gaseous substanceand at least one liquid substance. Furthermore, an electrophoreticeffect may occur which promotes the mobility of particles in the dermis.The method according to the invention can also be used to degrade,dislodge, rinse, wash out or otherwise render tattoo ink particles in atarget dermal region less discernible.

The method according to the invention allows the chemical properties oftattoo ink particles to be changed when they comes into contact with thegas bubbles of cold plasma. For example, biological structures in theskin or elsewhere, such as various cells, collagens, or other structuralproteins, can be influenced and treated. Non-biological material in theskin, such as tattoos or other foreign bodies, can be degraded orremoved.

The gaseous substance used in the method according to the invention maybe, for example, ambient air, a noble gas, oxygen, nitrogen, carbondioxide or a mixture of these gases. The liquid substance may be e.g.water, a salt solution, an alcohol, H₂O₂ or a mixture of the aboveliquids. Additives such as antibiotics, reactive monomers, surfactantsor foaming agents can also be added to the liquid substance.

In certain embodiments, discrete bubbles of the gaseous substance formin the liquid substance within the plasma discharge unit. Here the ratiobetween the proportion of the gaseous substance and the proportion ofthe liquid substance is controlled in such a way that individualdiscrete bubbles form within the liquid and are activated as a plasma orhighly active gas species. The temperature of this mixture of the liquidsubstance and the activated gaseous substance can be adjusted to adesired value by heating or cooling.

At least one component, the liquid or the gaseous component, can becollected after passing through the discharge zone and can be passed onto further use. The apparatus according to the invention can be adaptedor controlled to change the density and volume of the gaseous and/orliquid substances in the tubular discharge unit. The tubular dischargeunit can also be in the form of a capillary.

By means of the present invention, a discharge system can be used forheterogeneous mixtures of at least one gas and at least one liquid, oralso of special liquids without the admixture of a gas, to produceactive species in the gas or liquid phase. The active species can beused in various applications such as liquid sterilization, surfacetreatment, coating, human or animal skin treatment such as directsubepidermal CAP treatment, and many others.

In another non-limiting embodiment. as shown in FIG. 3 , the system fortattoo removal includes a main housing 100 wherein: an plasma generationcomponent 102; a fluid delivery component 104; and a fluid extractioncomponent 106 are integrated. In some other embodiments, the fluiddelivery component may be excluded from the system. The system isconnected and coupled to a free-standing treatment component 108, whichmay be in the form of pen or wand-like component. The housing of thetattoo removal system also includes additional components, as needed. topower the aforementioned 102, 104, and 106 components and the treatmentcomponent 108, so as to provide power from an electrical outlet or fromone or more battery source(s). The main housing may further include oneor more control unit(s), which may include input controls (i.e., knobs,buttons. foot pedals) and analog or digital displays which showparameters of the 102, 104, and 106 components in order to control andregulate each component's parameters prior to and during operation. Insome embodiments, one (main) control unit may be used to control all thecomponents, while in some other embodiments each component has its ownindividual control unit on the system's main housing.

In some other embodiments. the plasma generation component 102; a fluiddelivery component 104; and a fluid extraction component 106 may beincorporated into a single combined treatment component 106. In someembodiments. the fluid delivery component may be excluded from thecombined treatment component. A foot pedal 110 can provide means forcontrolling the plasma application, saline wash, and extraction.

FIG. 3A is a schematic illustration of a kinetic applicator 120 that canbe incorporated into the treatment components (handpieces) of theinvention, including a motor 122 and cam mechanism 124 to imparting avibratory or oscillating motion to the needle or active electrode 208.

The electrical power source component 64 may be a commercially availablecomponent which is adapted to be a part of the tattoo removal systemdescribed herein. The plasma generation component housed in the mainsystem includes all necessary components required to provide a highfrequency alternating current, or high repetition rate pulsed directcurrent to one or more skin-penetrating electrodes. Optional componentsrelating to cold plasma formation can also include, but are not limitedto, gas inputs, valves, regulators, pumps, gas mixing chamber/units,power systems. The conditions, such as the power. flow rate of gas(es),and the ratio of gases in mixtures used to generate a cold plasma can becontrolled as needed to achieve the desired properties of the coldplasma, using the input control(s) connected and coupled to the plasmageneration unit.

Typically, plasmas are generated from a gas or a mixture of gases whichmay include, but are not limited to, air, carbon dioxide, oxygen,nitrogen, helium, argon, neon, xenon, and krypton. In preferredembodiments, the cold plasma generation unit receives gas(es) from oneor more gas sources. In some embodiments, the one or more gas sourcesmay be in the form of free-standing replaceable gas tanks/cylinders orthe one or more gas(es) may be from a source such as a gas outletpresent on a wall and connected to a central gas source. In certainembodiments, the one or more gas sources are external to the mainhousing of the tattoo removal system and are coupled and connected tothe one or more gas inputs of the plasma generation component of thesystem by any suitable means (i.e., gas regulator and gas tubing). Incertain other embodiments, the one or more gas sources may be includedwithin the housing of the tattoo removal system, if desirable. Inpreferred embodiments the power used to generate the cold plasma is inthe range of about 80 W to about 150 W. In some preferred embodiments,the gas flow rates are in the range of about 0.00001 to about 15 Lmin⁻¹. The relative percentages of the one or more gases present in themixture can be controlled by a gas mixing unit to achieve any suitablerelative gas mix percentage necessary to achieve a cold plasma. Incertain embodiments, wherein the plasma generating mixture of gases iscomposed of oxygen mixed with argon or helium, the percentage of oxygenin the mixture is preferably in the range of about 0.1% to about 5%.

The plasma generation component is coupled and connected using anysuitable means and outputs/delivers the cold plasma generated to thetreatment component for delivery to the tattooed dermis. The cold plasmastream generated may be controlled via the one or more input controlunits of the system. The plasma output by the component to the treatmentcomponent may be a continuous cold plasma jet stream or a discontinuouspulsed cold plasma jet stream. It should be apparent that the detailsdescribed herein are non-limiting and that other suitable conditions andparameters can be selected and utilized in order to generate and deliverthe cold plasma to the tattooed dermis. The delivery of cold plasma tothe dermis via a treatment component, which may be in the form of apen/wand, can be controlled by a skilled/trained operator or technicianusing an input control unit, such as a foot pedal.

In some embodiments, the plasma generation component as discussed abovemay be incorporated directly into the treatment component. In certainembodiments, the plasma generated in the treatment component is an airplasma and requires no external gas source. In certain otherembodiments, one or more gas sources that are external to the treatmentcomponent are coupled and connected to one or more gas inputs of thetreatment component by any suitable means (i.e., gas regulator and gastubing). In certain other embodiments, the one or more gas sources maybe included within the treatment component, if desirable.

Fluid Delivery Component

The fluid delivery component of the system includes one or more fluidreservoir units which can hold one or more liquids to be mixed with theionized gas or to serve a separate mobilization fluid. The one or morereservoir units are coupled and connected to the treatment component ofthe tattoo removal system by any suitable means (i.e., tubing) in orderto output the mobilization fluid to the treatment component. Themobilization fluid delivery component includes one or more controllablefluid pumps which deliver the mobilization fluid to the treatmentcomponent at a controllable flow rate. The flow rate of the fluid can beregulated by the one or more input controls or units coupled andconnected to the fluid delivery component. In some embodiments themobilization fluid is not pre-formulated but can be generated on-demandby mixing units which may form part of the fluid delivery component.Such mixing units are fed by the one or more fluid reservoir units whichmay contain the component fluids and other agents which form the desiredmobilization fluid such as, but not limited to, sterile water, salinesolution, buffered aqueous solutions and suitable local anesthetics,anti-infective agents, antiseptic agents, anti-inflammatory agents, andcombinations thereof. The delivery of mobilization fluid to the dermisvia the treatment component can be controlled by a skilled/trainedoperator or technician using an input control unit, such as a footpedal.

In some other embodiments, the fluid delivery component, as describedabove. may be directly incorporated into a free-standing pen orwand-like component. In such embodiments, one or more disposable fluidcartridges which hold a given volume of pre-formulated mobilizationfluid (described above) may be coupled and connected to the fluiddelivery component to output the mobilization fluid to one or moreneedle or probe-like structures of the treatment component as describedbelow. In such embodiments, the delivery of mobilization fluid to thedermis via the one or more needle or probe-like structures of thetreatment component can be controlled by a skilled/trained operator ortechnician using an input control unit present on the treatmentcomponent.

Fluid Extraction Component

The fluid extraction component of the system includes one or more vacuumpumps and/or other components necessary for creating a vacuum or partialvacuum and is connected and coupled by any suitable means to thetreatment component so as to create suction used to extract themobilization fluid delivered to the dermis during tattoo removaltreatment and draw/extract the mobilization fluid containing dislodgedand degraded ink particles and by-products thereof, and tissueby-products thereof away from the dermis and surrounding tissues of thesubject. In some embodiments of the system which exclude a fluiddelivery component and mobilization fluid, the fluid extractioncomponent can remove the dislodged degraded tattoo ink particles whichmay be present in the natural fluids of the dermis or surrounding tissuedirectly. In some embodiments, suction created by the extractioncomponent is applied as a continuous suction or, alternatively, thesuction can be applied intermittently. The application of suction to thedermis and/or surrounding tissue can be controlled by a skilled/trainedoperator or technician using an input control unit, such as a footpedal.

In some other embodiments, the fluid extraction component, as describedabove, may be directly incorporated into a free-standing pen orwand-like component. In such embodiments, the application of suction tothe dermis and/or surrounding tissue can be controlled by askilled/trained operator or technician using an input control unitpresent on the treatment component, which may be in the form of a pen orwand.

Treatment Component

The treatment component can be coupled and connected to the componentsdiscussed above using any suitable means known. Alternatively, thetreatment component can have incorporated into it at least one or moreof components as described above. The treatment component can be in theform of a pen or wand 200 and is formed of a main body as shown in FIG.4 . The treatment component is also referred to herein as a pen/wandcomponent. The treatment component includes suitable mechanicalcomponents. as needed, to deliver electrical energy (and, optionally.cold plasma) and mobilization fluid into the dermis and to apply suctionto the dermis. One end 202 of the treatment component may include one ormore inputs and outputs (not shown) which are connected/coupled to theother components of the system as described above when these componentsare external to the treatment component. For example, the inputs canreceive the electrical energy and mobilization fluid and the output canreceive the mobilization or other body fluid extracted from the dermisor surrounding tissue during tattoo removal. The opposite end of thetreatment component includes a treatment end which can output anddeliver the activated liquid-gas mixture and/or mobilization fluid intothe dermis. The treatment end 204 can also receive extractedmobilization fluid, or other natural body fluids. which containdislodged and degraded tattoo ink particles during treatment of thedermis and surrounding tissue.

Kinetic Movement

In certain embodiments, the treatment end 204 is formed of a cartridgeunit 206 which contains one or more needle or probe-like structures 208which penetrate the subject's tattooed skin. The treatment end of thetreatment component includes one or more needle or probe-like objects208 which can penetrate skin and preferably form a part of a removable,disposable, and/or replaceable unit cartridge. The one or more needle orprobe-like structures 208 can be made of either plastic, metal or acombination thereof. In some non-limiting embodiments, the removable,disposable, and/or replaceable cartridge includes one, two, three, four,five, six, seven or more needles. The depth of penetration of the one ormore needle or probe-like structures, present in the needle cartridge,into the skin is preferably to the depth of the dermis of the subject'stattooed skin but may be adjusted by a skilled/trained operator ortechnician as needed to apply the tattoo removal treatment method usingthe system described herein. The one or more needle or probe-likestructures 208, which penetrate into the tattooed dermis, oscillate orpulse during tattoo removal treatment via a mechanical process, such asa piston like drive which pulses and/or oscillates the needles in andout of the dermis at varying speeds. In certain other embodiments, theone or more needle or probe-like structures 208, which penetrate intothe tattooed dermis are fixed and do not pulse or oscillate.

In some embodiments, the one or more needle or probe-like structuresoscillate or pulse and with each oscillation or pulse perform one ormore functions of delivering electrical energy, delivering cold plasma,delivering mobilization fluid to the dermis, or extracting themobilization fluid containing dislodged and degraded ink particles andby-products thereof, and tissue by-products thereof. In some embodimentseach full or partial oscillation or pulse applies a particular functionsequentially at a time and all the functions as described are performedso as to provide at least one complete cycle which includes thedislodgement, mobilization, and extraction steps. In certain otherembodiments, all of the functions are applied concurrently during agiven oscillation or pulse of the one or more needles. In some otherembodiments, some, but not necessarily all of, the functions describedform part of a cycle which is performed at least one or more timesduring a given oscillation or pulse of the one or more needles, asnecessary to remove the tattoo ink from the subject's dermis andrendering the tattoo undetectable, invisible, and/or non-discernible.

As shown in FIG. 4 . the one or more needle or probe-like structures 208which are present at the treatment end 204 of a treatment component inthe form of a pen/wand 200 can penetrate into the dermis and deliverelectrical energy (and, optionally, cold plasma) and deliver and extractfluids to and from the dermis and surrounding tissue undergoing tattooremoval. In some embodiments, different needle/probe-like objectspresent on the treatment end can serve different functions, such asplasma delivery, fluid delivery, or fluid extraction. In someembodiments, a single needle/probe-like object may perform multiple orall of the aforementioned functions.

As shown in FIGS. 4A and 4B, each of the needle or probe-like structuresof the removable. disposable, and/or replaceable unit cartridge can beformed of a multiple sheathed needle 300 which is formed from nestedmultiple concentric needles 302, 304, and 306.

In one non-limiting example as shown in the configuration of FIGS. 4Aand 4B, a multi-sheathed needle or probe-like 300 is formed of threeconcentric nested/embedded needle or probe-like structures forming inner306. middle 304, and outer rings 302. In some embodiments, the outermost ring 302 delivers cold plasma and optionally the outer most portionof the needle or probe-like structure includes suitable openings 308 onthe outer side for delivering cold plasma to the dermis. In someembodiments, the middle ring 304 delivers mobilization fluid to thedermis. In some embodiments, the inner most ring 302 provides suction tothe dermis to remove mobilization fluid containing dislodged anddegraded tattoo ink particles and by-products thereof from the dermis.Any one or all of the concentric structures can serve as the activeelectrode for delivery of electrical energy.

In another non-limiting example as shown in the configuration of FIGS.5A and 5B, a multi-sheathed needle 400 is formed of two concentricnested/embedded needle or probe-like structures forming inner 404 andouter 402 rings. In some embodiments, the outer most ring delivers coldplasma and extraction fluid which are sequentially pulsed into thedermis. Optionally. the outer most portion 402 of the needle orprobe-like structure can include suitable openings 406 on the outer sidefor delivering cold plasma to the dermis. In some embodiments. the innerring 404 provides suction to the dermis to remove mobilization fluidcontaining dislodged and degraded tattoo ink particles and by-productsthereof from the dermis. Again, anyone or both of the concentricstructures can serve as the active electrode for delivery of electricalenergy.

In another non-limiting example as shown in the configuration of FIGS.6A and 6B, a single-sheathed needle 500 may be used in the cartridge.Optionally, the outer surface of the needle or probe-like structure 500can include suitable openings 502 on the outer side for delivering coldplasma to the dermis. In a single sheath configuration, the cold plasma,mobilization fluid, and suction are sequentially applied to the dermisduring treatment and the sheath itself is conductive for delivery ofelectrical energy to the target tattoo region.

As described above, the one or more needle or probe-like structures ofthe cartridge may each be formed of a multiple sheathed needle-likestructure. One of ordinary skill will immediately recognize that theabove examples are non-limiting and variations are permitted regardingthe use of any of the sheaths present in the embedded/nested structureto achieve any of the plasma, fluid, or extraction functions asdescribed above. In some embodiments, the rate of flow of cold plasma,mobilization fluid and rate of suction can be controlled by acomputerized flow meter included in the treatment component.

In some embodiments, an input control, such as a foot pedal or button(s)present on the treatment component. may be used to activate, deactivate,and control all of electrical energy, cold plasma, dislodgement,mobilization and extraction components coupled and connected to thetreatment component, or integrated within the treatment component whichmay be in the form of a pen/wand, at one time or may control theelectrical energy. cold plasma, dislodgement, mobilization andextraction components individually. In some other embodiments, an inputcontrol, such as a foot pedal and/or button(s) present on the treatmentcomponent, can be used initiate a cycle which triggers each function ofa given component in a given sequence (i.e., component 100, thencomponent 102, and subsequently component 104). The cycle/sequence maybe repeated at any suitable interval of time and for any suitable numberof cycles as needed to remove the tattoo from the subject's dermis andsurrounding tissue.

The application of electrical energy, plasma, mobilization fluid, and/orextraction (i.e., suction) through the one or more needle/probe-likestructures present on the treatment end to the tattooed dermis andsurrounding tissue can be controlled by a skilled/trained operator ortechnician with high precision. In preferred embodiments, theskilled/trained operator or technician can activate or deactivate thedifferent functions of the system components individually or incombination using one or more input control unit(s), such as a footpedal or button(s) present on the treatment component. In someembodiments, the operator/technician may apply electrical energy anddepending on the extent to which the tattoo has been renderedundetectable, invisible, and/or non-discernible determine not to applycold plasma, a mobilization fluid and actuate extraction. In certainother embodiments, the operator/technician may choose to further apply amobilization fluid and extraction in order to further render the tattooundetectable, invisible, and/or non-discernible. In yet anotherembodiment, the operator/technician may choose to only further applyextraction to remove dislodged and degraded tattoo ink particles,degradation by-products thereof, and/or tissue by-products thereofcontained in bodily fluid without applying a mobilization fluid.

Electric Field Generating Component

FIGS. 7A-7C illustrate the use of F-CAP together with an array ofelectrodes separated from each other to achieve a generally uniformelectric field strength over at least a portion of a target region byoverlapping fields. FIG. 7A illustrates two electrodes of such an array(701, 702) and their respective electric fields (710, 720)—and theirregion of overlap (730) when electrical energy is applied to theindividual electrodes. FIG. 7B is a graph of electrical field intensityversus distance from each of electrodes 701 and 702 and furtherillustrating (by a dotted line) an increased field uniformity due to theoverlapping fields. FIG. 7C illustrates a multi-electrode array 700 withelectrodes in a “honeycomb” arrangement to further enhance fielduniformity.

Alternative Embodiments

FIG. 8 illustrates another embodiment of the invention, in which apiezoelectric plasma generating system 80 includes controller 82, switch(foot petal) 81, syringe pumps 84A and 84B, syringes 86A and 86B andplasma delivery handpiece 88. The syringe pumps 84A and 84B can be usedto deliver a pretreatment mobilization fluid to the target tattoo regionas well as to deliver mobilization fluid during the application ofplasma. For example, one syringe pump can deliver a liquid withentrained gas, e.g., water with dissolved carbon dioxide, such that theplasma generator can induce formation of an activated liquid gas mixturewith plasma gas bubbles. One or both of the syringe pumps can also beactivated in reverse to extract fluid with degraded tattoo particlesfollowing plasma treatment of the dermal region.

FIG. 9 illustrates yet another embodiment of the invention, in which adielectric barrier plasma generating system 90 is shown including highvoltage source 92, liquid pump 94, controller 96, display 98 and switch95. They system 90 can further include a pressurized gas source 91 and aliquid source 93. In this system a gas, such as argon, neon, or othernoble gas or air, can be delivered to a plasma generator as describedabove in FIG. 2 where the gas can ignited by the dielectric barrierelectrode to create a plasma. The plasma can be mixed with liquid fromthe liquid source 93 in the plasma generator and then delivered asliquid entrained plasma gas bubbles to the target tattoo region.

Example 1

This example describes application of both cold atmospheric plasma (CAP)and fluid cold atmospheric plasma (F-CAP). The CAP treatment wasdelivered by electrically activating a gas (air) and injecting theresulting cold atmospheric plasma into a tattooed region of a rat. TheF-CAP treatment involved forming plasma gas bubbles in a liquid (carbondioxide infused water) and injecting this activated mixture into thesame tattooed region.

This animal experiment followed IACUC protocols. The animal (six monthsold, weighing 880 grams) had been tattooed six-months previously using aviolet-black tattoo ink (Millennium Mom's Ink) to form a linear tattooto be treated and an adjacent control tattoo (dot shaped).

The CAP and F-CAP treatments were preceded by a pretreatment injectionof a mobilization fluid. The mobilization fluid (distilled water) wasfirst injected into the mouse's dermal target region of the tattoo. A 27Gauge needle (Becton Dickson) and a 5 ml syringe were used to performfive pretreatment injections of the mobilization fluid in a pattern thatspanned the length of the linear tattoo. Following the injections, five“blebs” were visible at the skin surface.

A piezoelectric-driven plasma generator with a distal needle injectorwas then used to apply the CAP. Fifteen lateral injections of the plasma(electrically activated air) were applied along the length of thetattoo.

Following the CAP treatment, external suction was applied using anOiiwak dermatological vacuum applicator. Vacuum was applied 10 timesacross the CAP treated area for several seconds per each application.

The same animal then underwent a F-CAP treatment with the samepiezoelectric plasma generator with a two needle delivery head. Thefluid was carbon dioxide infused water. Electrical excitation of thethis liquid-gas mixture induced plasma gas bubbles. Twenty injectionswere delivered.

Following Fluid-CAP, external suction was again performed using theOiiwak dermatological vacuum applicator. Vacuum was applied five timesacross the CAP treated area for several minutes per each application.

The progress of the treatment was followed for a month. By day 32, therewas a noticeable diminution in tattoo visibility and the skin had healedwith no scarring. An untreated control dot of ink was clearly visiblebut the treated linear tattoo was essentially non-discernible. Theanimal was euthanized 6 weeks after treatment. Histology of the mouse'sdermis revealed only rare ink particles could be found under microscopicinvestigation in the treated tattoo region.

Example 2

In this experiment, cold atmospheric plasma (CAP) formed by excitationof an inert gas (neon) was again followed by fluid-assisted coldatmospheric plasma (F-CAP). The plasma was induced in both treatments bya dielectric barrier discharge plasma generator. The F-CAP treatment, inthis instance, involved electrically activating a mixture of neon gasand carbon-dioxide infused water and injecting the resulting fluid withentrained gas bubbles of cold atmospheric plasma into a tattooed regionof a rat.

The animal experiment was again conducted according to IACUC protocols.The animal (mouse, approximated seven months old, weighing 1.2kilograms) had been tattooed using a violet-black tattoo ink (MillenniumMom's Ink) six months earlier to form a linear tattoo and a control dottattoo before the treatment.

The animal in this case was also pretreated with a mobilization fluid(distilled water), which was first injected into target region of thetattoo using a 30 Gauge needle and a syringe. Three injections of themobilization fluid in a pattern that spanned the length of the lineartattoo. Following the injections, “blebs” were visible at the skinsurface.

The CAP treatment involved 15 lateral injections of neon gas plasma withan exposure of several seconds per injection. The CAP treatment wasdirectly followed by an F-CAP treatment.

For the F-CAP treatment, an activated liquid-gas mixture (Neon andcarbon dioxide infused water) was injected via a dielectric barrierplasma generating handpiece attached to 23 Gauge needle. Fifteen lateralinjections were delivered with a few seconds exposure dose per injectionand estimated fluid injection of 15 milliliters.

Following this Fluid-CAP treatment, external suction was performs usingthe Oiiwak dermatological vacuum applicator. Vacuum was applied threetimes across the CAP treated area for 1 minutes per each application.

The progress of the treatment was again followed and there was anoticeable diminution in tattoo visibility and the skin had healed withno scarring.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meanings as commonly understood by one of skill in the artto which the present teachings belong. All patents, patent applicationsand publications of any kind cited herein and the materials for whichthey are cited are specifically incorporated by reference in theirentirety.

It should be understood that any method step or element described hereincan be used in conjunction with any other method or element,respectively, whether or not such combination is described in a specificexample or embodiment. All such permutations are embraced as part andparcel of the present invention.

Within this specification, embodiments have been described in a way thatenables a clear and concise specification to be written, but it isintended and will be appreciated that embodiments may be variouslycombined or separated without departing from the invention. For example,it will be appreciated that all preferred features (element or methodstep) described and/or claimed are applicable to all aspects of theinvention described herein. Every claimed feature should be deemedcapable of multiple dependencies from other claimed features even ifonly one dependency is recited unless the combination of features isphysically impossible.

Those skilled in the art will recognize, or be able to ascertain usingno more than routine experimentation, many equivalents to the specificembodiments of the exemplary teachings described herein. Suchequivalents are also intended to be encompassed by the following claims.

We claim:
 1. A system for removing a tattoo from a subject's skin, thesystem comprising: a gas source for providing a gas, a liquid source forproviding a liquid, a plasma generator for receiving the gas and liquidand generating an activated liquid-gas mixture comprising the liquidwith plasma gas bubbles, and a conduit for delivery of the activatedliquid-gas mixture to a target tattooed region.
 2. The system of claim1, further comprising a mobilization liquid delivery component fordelivering a mobilization liquid either from the liquid source or froman alternative liquid source to the target tattoo region either before,during or after delivery of the activated liquid-gas mixture.
 3. Thesystem of claim 2, wherein the mobilization fluid delivery componentfurther comprises a syringe and a needle for delivery of themobilization fluid.
 4. The system of claim 1, further comprising anextraction component.
 5. The system of claim 4, wherein the extractioncomponent is configured to apply suction to the target tattooed regionduring or after application of the activated liquid-gas mixture.
 6. Thesystem of claim 1, further comprising a treatment applicator configuredto pierce skin and deliver the activated liquid-gas mixture to thetattooed region.
 7. The system of claim 6, wherein the treatmentapplicator comprises a hollow needle with a tip from which the activatedliquid-gas mixture can be applied to the target tattooed region.
 8. Thesystem of claim 7, wherein the hollow needle comprises a multiplesheathed needle.
 9. The system of claim 6, wherein the treatmentapplicator comprises a cartridge unit with one or more needlesconfigured to penetrate the skin associated with the tattooed region.10. The system of claim 9, wherein the cartridge unit is replaceable.